Solubilized Cartilage ECM Facilitates the Recruitment and Chondrogenesis of Endogenous BMSCs in Collagen Scaffolds for Enhancing Microfracture Treatment

Articular cartilage has very poor intrinsic healing ability and its repair remains a significant clinical challenge. To promote neocartilage regeneration, we fabricated two collagen (Col) scaffolds functionalized with a porcine decellularized extracellular matrix (dECM) in the forms of particle and solution named pE-Col and sE-Col, respectively. Their differences were systematically compared, including the biochemical compositions, scaffold properties, cell-material interactions, and in situ cartilage regeneration. While it is demonstrated that both forms of dECM could enhance the cell recruitment, proliferation, and chondrogenesis of bone marrow stem cells (BMSCs) in vitro, better performance was seen in the sE-Col group, which could quickly provide a more favorable chondrogenic microenvironment for endogenous BMSCs. The superiority of sE-Col was also proved by our in vivo study, which showed that the sE-Col scaffold achieved better structural hyaline-like neocartilage formation and subchondral bone repair compared to the pE-Col scaffold, according to the gross morphology, biological assessment, and micro-CT imaging analysis. Together, this study suggests that the sE-Col scaffold holds great potential in developing the one-step microfracture-based strategy for cartilage repair and also reminds us that despite dECM being a promising biomaterial in tissue engineering, the optimization of the proper processing methodology would be a crucial consideration in the future design of dECM-based scaffolds in articular cartilage regeneration.